Aging is a multifaceted and complicated process, manifested by a decline of normal physiological functions across tissues and organs, leading to overt frailty, mortality, and chronic diseases, such as skeletal, cardiovascular, and cognitive disorders, necessitating the development of practical therapeutic approaches. Stem cell aging is one of the leading theories of organismal aging. For decades, mesenchymal stem/stromal cells (MSCs) have been regarded as a viable and ideal source for stem cell-based therapy in anti-aging treatment due to their outstanding clinical characteristics, including easy accessibility, simplicity of isolation, self-renewal and proliferation ability, multilineage differentiation potentials, and immunomodulatory effects. Nonetheless, as evidenced in numerous studies, MSCs undergo functional deterioration and gradually lose stemness with systematic age in vivo or extended culture in vitro, limiting their therapeutic applications. Even though our understanding of the processes behind MSC senescence remains unclear, significant progress has been achieved in elucidating the aspects of the age-related MSC phenotypic changes and possible mechanisms driving MSC senescence. In this review, we aim to summarize the current knowledge of the morphological, biological, and stem-cell marker alterations of aging MSCs, the cellular and molecular mechanisms that underlie MSC senescence, the recent progress made regarding the innovative techniques to rejuvenate senescent MSCs and combat aging, with a particular focus on the interplay between aging MSCs and their niche as well as clinical translational relevance. Also, we provide some promising and novel directions for future research concerning MSC senescence.

Mesenchymal stem cells (MSCs) could be identified in mammalian teeth. Currently, dental-derived MSCs (DMSCs) has become a collective term for all the MSCs isolated from dental pulp, periodontal ligament, dental follicle, apical papilla, and even gingiva. These DMSCs possess similar multipotent potential as bone marrow-derived MSCs, including differentiation into cells that have the characteristics of odontoblasts, cementoblasts, osteoblasts, chondrocytes, myocytes, epithelial cells, neural cells, hepatocytes, and adipocytes. Besides, DMSCs also have powerful immunomodulatory functions, which enable them to orchestrate the surrounding immune microenvironment. These properties enable DMSCs to have a promising approach in injury repair, tissue regeneration, and treatment of various diseases. This review outlines the most recent advances in DMSCs’ functions and applications and enlightens how these advances are paving the path for DMSC-based therapies.

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Strategies for therapeutic cell transplantation have been assessed for use in the treatment of massive peripheral nerve defects. To support safe and efficient cell transplantation, we have focused on the purification of cells using cell surface markers. Our group previously reported low-affinity nerve growth factor receptor (LNGFR)- and thymocyte antigen-1 (THY-1)-positive neural crest-like cells (LT-NCLCs), generated from human induced pluripotent stem cells (hiPSCs). In the present study, we investigated the efficacy of transplantation of hiPSC-derived LT-NCLCs in a murine massive peripheral nerve defect model. Animals with a sciatic nerve defect were treated with a bridging silicone tube prefilled with LT-NCLCs or medium in the transplantation (TP) and negative control (NC) groups, respectively. The grafted LT-NCLCs survived and enhanced myelination and angiogenesis, as compared to the NC group. Behavioral analysis indicated that motor functional recovery in the TP group was superior to that in the NC group, and similar to that in the autograft (Auto) group. LT-NCLCs promoted axonal regrowth and remyelination by Schwann cells. Transplantation of LT-NCLCs is a promising approach for nerve regeneration treatment of massive peripheral nerve defects.

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